Osteopontin Enhances Phagocytosis through a Novel Osteopontin Receptor, the αXβ2 Integrin

Schack, Lotte; Stapulionis, Romualdas; Christensen, Brian; Kofod-Olsen, Emil; Sørensen, Uffe B. Skov; Vorup-Jensen, Thomas; Sørensen, Esben S.; Höllsberg, Per

doi:10.4049/jimmunol.0900065

Cited by 93 publications

(93 citation statements)

References 48 publications

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“…Several receptors for osteopontin have been identifi ed in several cell types for a variety of physiological mechanisms, such as proliferation, differentiation and chemotaxis. For example, αXβ2 integrin functions as an OPN receptor for chemotaxis in monocytes (Schack et al, 2009), while OPN mediates metastasis via integrin αVβ3 and CD44 in tumor cells (Robertson et al, 2010). In this study, we found that expression of integrin α9 is notably increased in HSC by treatment of OPN.…”

Section: Discussionsupporting

confidence: 54%

Protein Expression Analysis in Hematopoietic Stem Cells during Osteopontin-Induced Differentiation of Natural Killer Cells

Kim¹,

Bae²,

Kim³

et al. 2011

Biomolecules and Therapeutics

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Natural Killer (NK) cells are the lymphocytes that are derived from hematopoietic stem cells, developed in the bone marrow from hematopoietic stem cells (HSC) by sequential acquisition of functional surface receptors, and express the repertoire of inhibitory and activating receptors. Recently, Osteopontin (OPN) has been identifi ed as a critical factor for differentiation of natural killer cells. However, the detailed mechanism of OPN-induced NK differentiation has been still to be elucidated. Here, we determined the signaling pathway and possible receptor for OPN in NK differentiation. OPN induced expression of Bcl-2 and activation of Erk kinase. Inhibition of Erk pathway decreased the effect of OPN on NK differentiation. In addition, the expression of integrin α9 was signifi cantly increased by OPN during NK differentiation, suggesting the possible role of a major signaling molecule for OPN-induced NK differentiation. (Chung et al., 2008). OPN is a secreted protein which is mainly expressed in bone marrow stromal cells. OPN has been known to play a variety of roles in cellular mechanisms including proliferation, apoptosis, and migration. In addition, OPN has been reported to act as a negative regulator of HSC although the effect of OPN on HSC proliferation or apoptosis is controversial. For example, it was shown that OPN reduces the number of HSCs by inhibition of proliferation while increasing apoptosis (Stier et al., 2005). On the contrary, it has been reported that OPN negatively regulates HSC proliferation in-

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Section: Discussionsupporting

confidence: 54%

Protein Expression Analysis in Hematopoietic Stem Cells during Osteopontin-Induced Differentiation of Natural Killer Cells

Kim¹,

Bae²,

Kim³

et al. 2011

Biomolecules and Therapeutics

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“…The αxβ2 integrin might serve such a function because it is abundantly expressed on macrophages and documented to promote murine macrophage phagocytosis (Schack et al . 2009). …”

Section: Discussionmentioning

confidence: 99%

OPN‐a induces muscle inflammation by increasing recruitment and activation of pro‐inflammatory macrophages

Many

Yokosaki

Uaesoontrachoon

et al. 2016

Experimental Physiology

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New Findings What is the central question of this study? What is the functional relevance of OPN isoform expression in muscle pathology? What is the main finding and its importance? The full‐length human OPN‐a isoform is the most pro‐inflammatory isoform in the muscle microenvironment, acting on macrophages and myoblasts in an RGD‐integrin‐dependent manner. OPN‐a upregulates expression of tenascin‐C (TNC), a known Toll‐like receptor 4 (TLR4) agonist. Blocking TLR4 signalling inhibits the pro‐inflammatory effects of OPN‐a, suggesting that a potential mechanism of OPN action is by promoting TNC–TLR4 signalling. Although osteopontin (OPN) is an important mediator of muscle remodelling in health and disease, functional differences in human spliced OPN variants in the muscle microenvironment have not been characterized. We thus sought to define the pro‐inflammatory activities of human OPN isoforms (OPN‐a, OPN‐b and OPN‐c) on cells present in regenerating muscle. OPN transcripts were quantified in normal and dystrophic human and dog muscle. Human macrophages and myoblasts were stimulated with recombinant human OPN protein isoforms, and cytokine mRNA and protein induction was assayed. OPN isoforms were greatly increased in dystrophic human (OPN‐a > OPN‐b > OPN‐c) and dog muscle (OPN‐a = OPN‐c). In healthy human muscle, mechanical loading also upregulated OPN‐a expression (eightfold; P < 0.01), but did not significantly upregulate OPN‐c expression (twofold; P > 0.05). In vitro, OPN‐a displayed the most pronounced pro‐inflammatory activity among isoforms, acting on both macrophages and myoblasts. In vitro and in vivo data revealed that OPN‐a upregulated tenascin‐C (TNC), a known Toll‐like receptor 4 (TLR4) agonist. Inhibition of TLR4 signalling attenuated OPN‐mediated macrophage cytokine production. In summary, OPN‐a is the most abundant and functionally active human spliced isoform in the skeletal muscle microenvironment. Here, OPN‐a promotes pro‐inflammatory signalling in both macrophages and myoblasts, possibly through induction of TNC–TLR4 signalling. Together, our findings suggest that specific targeting of OPN‐a and/or TNC signalling in the damaged muscle microenvironment may be of therapeutic relevance.

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“…It is present in elevated concentrations in human breast milk (~140 mg/L) [10] and has been found to have a positive influence on the development of the human immune system [11], as well as on the intestinal gene expression in rhesus monkeys [12]. OPN was shown to bind different strains of Staphylococcus aureus and Streptococcus agalactiae and opsonize them for phagocytosis [13], but except for this finding and the results mentioned above, little is known about the interaction between osteopontin and bacteria. In particular, it is not yet understood how OPN interferes with adhesion, and if the effect is a general phenomenon that applies to other bacteria in the oral cavity.…”

Section: Introductionmentioning

confidence: 99%

Osteopontin adsorption to Gram-positive cells reduces adhesion forces and attachment to surfaces under flow

Kristensen

Zeng

Neu

et al. 2017

Journal of Oral Microbiology

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The bovine milk protein osteopontin (OPN) may be an efficient means to prevent bacterial adhesion to dental tissues and control biofilm formation. This study sought to determine to what extent OPN impacts adhesion forces and surface attachment of different bacterial strains involved in dental caries or medical device-related infections. It further investigated if OPN's effect on adhesion is caused by blocking the accessibility of glycoconjugates on bacterial surfaces. Bacterial adhesion was determined in a shear-controlled flow cell system in the presence of different concentrations of OPN, and interaction forces of single bacteria were quantified using single-cell force spectroscopy before and after OPN exposure. Moreover, the study investigated OPN's effect on the accessibility of cell surface glycoconjugates through fluorescence lectin-binding analysis. OPN strongly affected bacterial adhesion in a dose-dependent manner for all investigated species (Actinomyces naeslundii, Actinomyces viscosus, Lactobacillus paracasei subsp. paracasei, Staphylococcus epidermidis, Streptococcus mitis, and Streptococcus oralis). Likewise, adhesion forces decreased after OPN treatment. No effect of OPN on the lectin-accessibility to glycoconjugates was found. OPN reduces the adhesion and adhesion force/energy of a variety of bacteria and has a potential therapeutic use for biofilm control. OPN acts upon bacterial adhesion without blocking cell surface glycoconjugates. ARTICLE HISTORY

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Osteopontin Enhances Phagocytosis through a Novel Osteopontin Receptor, the αXβ2 Integrin

Cited by 93 publications

References 48 publications

Protein Expression Analysis in Hematopoietic Stem Cells during Osteopontin-Induced Differentiation of Natural Killer Cells

Protein Expression Analysis in Hematopoietic Stem Cells during Osteopontin-Induced Differentiation of Natural Killer Cells

OPN‐a induces muscle inflammation by increasing recruitment and activation of pro‐inflammatory macrophages

Osteopontin adsorption to Gram-positive cells reduces adhesion forces and attachment to surfaces under flow

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